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Molecular basis of RNA function

RNA功能的分子基础

基本信息

批准号：
09278102
负责人：
NAKAMURA Yoshikazu
金额：
$ 132.1万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research on Priority Areas (A)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09278102/
关键词：
RNA translational control posttranscriptional control ribosome molecular mimicry stop codon life of mRNA RNA-binding protein 終止コドン

项目摘要

RNA plays a fundamental key role in life as a variety of regulatory and catalytic molecules involved in gene expression and cellular regulation. Here, we have studies molecular bases of dynamic RNA functions by focusing on RNA-protein complexes, regulatory RNAs for gene expression, splicing, transport and translation. The remarkable progress in functional and structural biology of translational apparatus has uncovered a novel biological phenomenon of macromolecular mimicry between protein and tRNA. The 3D struetures of translational elongation factor EF-G and ribosome recycling factor RRF are shown to mimic a tRNA shape. Another, even more sophisticated, example may be polypeptide release factors that are shown to possess a tripeptide 'anticodon' to decipher stop codons in mRNA, showing an impressive mimic of tRNA function. It is surprising that it took 4 decades since the discovery of the genetic code to figure out the basic mechanisms behind the deciphering of its 64 codons. Other achievements in the translational control - such as mammalian frameshift control, trans-translation with tmRNA in bacteria, and cell proliferation induced by the abnormality in the mammalian translation initiation factors - as well as in mRNA export, RNA-binding proteins involved in cell differentiation and RNA-protein complex structures, have uncovered numerous novel mechanisms of gene expression and RNA functions. These accomplishments clearly emphasized the biological importance and interest of the regulatory role of RNA and the mechanisms underlying the post-transcriptional control of gene expression. Certainly, understanding of RNA information flow has increasing importance in the post-genome era. A future emerging understanding of spatiotemporal networking of diverse functional RNAs Will greatly facilitate post-genome research as well as structural biology, while expanding our knowledge of how deeply and universally RNA constitutes life.

RNA作为参与基因表达和细胞调节的各种调节和催化分子在生命中起着基本的关键作用。在这里，我们研究了动态RNA功能的分子基础，重点是RNA-蛋白质复合物，基因表达，剪接，运输和翻译的调控RNA。翻译器的功能和结构生物学研究的显著进展揭示了蛋白质和tRNA之间的大分子拟态这一新的生物学现象。翻译延伸因子EF-G和核糖体再循环因子RRF的3D结构显示为模仿tRNA形状。另一个更复杂的例子可能是多肽释放因子，它们显示出具有三肽“反密码子”来破译mRNA中的终止密码子，显示出令人印象深刻的tRNA功能模拟物。令人惊讶的是，自从发现遗传密码以来，花了40年的时间才弄清楚破译其64个密码子背后的基本机制。在翻译控制方面的其他成就-如哺乳动物移码控制、细菌中tmRNA的反式翻译、哺乳动物翻译起始因子异常诱导的细胞增殖-以及在mRNA输出、参与细胞分化的RNA结合蛋白和RNA-蛋白质复合物结构方面的成就，揭示了许多基因表达和RNA功能的新机制。这些成就清楚地强调了RNA的调节作用和基因表达的转录后控制机制的生物学重要性和意义。当然，理解RNA信息流在后基因组时代越来越重要。未来对不同功能RNA的时空网络的理解将极大地促进后基因组研究和结构生物学，同时扩大我们对RNA构成生命的深度和普遍性的认识。